The mechanisms of microgliosis and pain following peripheral nerve injury

Experimental Neurology

Volumn 234, Issue 2, 2012, Pages 271-282

  Calvo, Margarita ^a   Bennett, David L H ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Microglia; Neuropathic pain; Peripheral nerve injury

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 3; CATHEPSIN S; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR3; FRACTALKINE; GAMMA INTERFERON; GELATINASE B; MONOCYTE CHEMOTACTIC PROTEIN 1; NEU DIFFERENTIATION FACTOR; OXALIPLATIN; PACLITAXEL; PATTERN RECOGNITION RECEPTOR; PURINERGIC P2X RECEPTOR; PURINERGIC P2Y RECEPTOR; SECONDARY LYMPHOID TISSUE CHEMOKINE; VINCRISTINE; ZALCITABINE;

ANTIGEN PRESENTATION; CANCER PAIN; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; CYTOKINE RELEASE; DIABETIC NEUROPATHY; DIMERIZATION; GLIOSIS; HUMAN; HYPERGLYCEMIA; LOW DRUG DOSE; MICROGLIA; NEUROPATHIC PAIN; NEUROPATHY; NONHUMAN; PATHOGENESIS; PERIPHERAL NERVE INJURY; PERIPHERAL NEUROPATHY; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SPINAL GANGLION; UPREGULATION;

ANIMALS; CHEMOKINES; CYTOKINES; GLIOSIS; MICROGLIA; NEURALGIA; PERIPHERAL NERVE INJURIES; SPINAL CORD;

EID: 84858152101     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2011.08.018     Document Type: Review

References (153)

1. Abbadie C., Lindia J.A., Cumiskey A.M., Peterson L.B., Mudgett J.S., Bayne E.K., DeMartino J.A., MacIntyre D.E., Forrest M.J. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:7947-7952.
2. Ajami B., Bennett J.L., Krieger C., Tetzlaff W., Rossi F.M. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 2007, 10:1538-1543.
3. Akiyama H., McGeer P.L. Brain microglia constitutively express beta-2 integrins. J. Neuroimmunol. 1990, 30:81-93.
4. Alexander G.M., Perreault M.J., Reichenberger E.R., Schwartzman R.J. Changes in immune and glial markers in the CSF of patients with complex regional pain syndrome. Brain Behav. Immun. 2007, 21:668-676.
5. Backonja M.M., Coe C.L., Muller D.A., Schell K. Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain patients. J. Neuroimmunol. 2008, 195:157-163.
6. Bacon K., Baggiolini M., Broxmeyer H., Horuk R., Lindley I., Mantovani A., Maysushima K., Murphy P., Nomiyama H., Oppenheim J., Rot A., Schall T., Tsang M., Thorpe R., Van D.J., Wadhwa M., Yoshie O., Zlotnik A., Zoon K. Chemokine/chemokine receptor nomenclature. J. Interferon Cytokine Res. 2002, 22:1067-1068.
7. Banati R.B., Cagnin A., Brooks D.J., Gunn R.N., Myers R., Jones T., Birch R., Anand P. Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury. Neuroreport 2001, 12:3439-3442.
8. Beggs S., Salter M.W. Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury. Brain Behav. Immun. 2007, 21:624-633.
9. Bennett G.J., Xie Y.K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988, 33:87-107.
10. Bhat N.R., Zhang P., Lee J.C., Hogan E.L. Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression in endotoxin-stimulated primary glial cultures. J. Neurosci. 1998, 18:1633-1641.
11. Biber K., Sauter A., Brouwer N., Copray S.C., Boddeke H.W. Ischemia-induced neuronal expression of the microglia attracting chemokine secondary lymphoid-tissue chemokine (SLC). Glia 2001, 34:121-133.
12. Biber K., Tsuda M., Tozaki-Saitoh H., Tsukamoto K., Toyomitsu E., Masuda T., Boddeke H., Inoue K. Neuronal CCL21 up-regulates microglia P2X4 expression and initiates neuropathic pain development. EMBO J. 2011, 30:1864-1873.
13. Blinzinger K., Kreutzberg G. Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z. Zellforsch. Mikrosk. Anat. 1968, 85:145-157.
14. Calvo M., Zhu N., Grist J., Ma Z., Loeb J.A., Bennett D.L. Following nerve injury neuregulin-1 drives microglial proliferation and neuropathic pain via the MEK/ERK pathway. Glia 2011, 59:554-568.
15. Calvo M., Zhu N., Tsantoulas C., Ma Z., Grist J., Loeb J.A., Bennett D.L. Neuregulin-ErbB signaling promotes microglial proliferation and chemotaxis contributing to microgliosis and pain after peripheral nerve injury. J. Neurosci. 2010, 30:5437-5450.
16. Cao L., DeLeo J.A. CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur. J. Immunol. 2008, 38:448-458.
17. Cao L., Palmer C.D., Malon J.T., De Leo J.A. Critical role of microglial CD40 in the maintenance of mechanical hypersensitivity in a murine model of neuropathic pain. Eur. J. Immunol. 2009, 39:3562-3569.
18. Chakraborty S., Kaushik D.K., Gupta M., Basu A. Inflammasome signaling at the heart of central nervous system pathology. J. Neurosci. Res. 2010, 88:1615-1631.
19. Clark A.K., D'Aquisto F., Gentry C., Marchand F., McMahon S.B., Malcangio M. Rapid co-release of interleukin 1beta and caspase 1 in spinal cord inflammation. J. Neurochem. 2006, 99:868-880.
20. Clark A.K., Staniland A.A., Marchand F., Kaan T.K., McMahon S.B., Malcangio M. P2X7-dependent release of interleukin-1beta and nociception in the spinal cord following lipopolysaccharide. J. Neurosci. 2010, 30:573-582.
21. Clark A.K., Wodarski R., Guida F., Sasso O., Malcangio M. Cathepsin S release from primary cultured microglia is regulated by the P2X7 receptor. Glia 2010, 58:1710-1726.
22. Clark A.K., Yip P.K., Grist J., Gentry C., Staniland A.A., Marchand F., Dehvari M., Wotherspoon G., Winter J., Ullah J., Bevan S., Malcangio M. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:10655-10660.
23. Clark A.K., Yip P.K., Malcangio M. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J. Neurosci. 2009, 29:6945-6954.
24. Colburn R.W., DeLeo J.A., Rickman A.J., Yeager M.P., Kwon P., Hickey W.F. Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat. J. Neuroimmunol. 1997, 79:163-175.
25. Colburn R.W., Rickman A.J., DeLeo J.A. The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp. Neurol. 1999, 157:289-304.
26. Costigan M., Moss A., Latremoliere A., Johnston C., Verma-Gandhu M., Herbert T.A., Barrett L., Brenner G.J., Vardeh D., Woolf C.J., Fitzgerald M. T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J. Neurosci. 2009, 29:14415-14422.
27. Coull J.A., Beggs S., Boudreau D., Boivin D., Tsuda M., Inoue K., Gravel C., Salter M.W., De K.Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005, 438:1017-1021.
28. Courteix C., Eschalier A., Lavarenne J. Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain. Pain 1993, 53:81-88.
29. Coyle D.E. Partial peripheral nerve injury leads to activation of astroglia and microglia which parallels the development of allodynic behavior. Glia 1998, 23:75-83.
30. Cross A.K., Woodroofe M.N. Chemokines induce migration and changes in actin polymerization in adult rat brain microglia and a human fetal microglial cell line in vitro. J. Neurosci. Res. 1999, 55:17-23.
31. de Jong E.K., Dijkstra I.M., Hensens M., Brouwer N., van A.M., Liem R.S., Boddeke H.W., Biber K. Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion. J. Neurosci. 2005, 25:7548-7557.
32. Daulhac L., Mallet C., Courteix C., Etienne M., Duroux E., Privat A.M., Eschalier A., Fialip J. Diabetes-induced mechanical hyperalgesia involves spinal mitogen-activated protein kinase activation in neurons and microglia via N-methyl-D-aspartate-dependent mechanisms. Mol. Pharmacol. 2006, 70(4):1246-1254.
33. Daulhac L., Maffre V., Mallet C., Etienne M., Privat A.M., Kowalski-Chauvel A., Seva C., Fialip J., Eschalier A. Phosphorylation of spinal N-methyl-d-aspartate receptor NR1 subunits by extracellular signal-regulated kinase in dorsal horn neurons and microglia contributes to diabetes-induced painful neuropathy. Eur. J. Pain 2011, 15(2):169.e1-169.e12.
34. Decosterd I., Woolf C.J. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain 2000, 87:149-158.
35. Del V.L., Schwartzman R.J., Alexander G. Spinal cord histopathological alterations in a patient with longstanding complex regional pain syndrome. Brain Behav. Immun. 2009, 23:85-91.
36. Dore-Savard L., Otis V., Belleville K., Lemire M., Archambault M., Tremblay L., Beaudoin J.F., Beaudet N., Lecomte R., Lepage M., Gendron L., Sarret P. Behavioral, medical imaging and histopathological features of a new rat model of bone cancer pain. PLoS One 2010, 5:e13774.
37. Echeverry S., Shi X.Q., Zhang J. Characterization of cell proliferation in rat spinal cord following peripheral nerve injury and the relationship with neuropathic pain. Pain 2008, 135:37-47.
38. Eriksson N.P., Persson J.K., Svensson M., Arvidsson J., Molander C., Aldskogius H. A quantitative analysis of the microglial cell reaction in central primary sensory projection territories following peripheral nerve injury in the adult rat. Exp. Brain Res. 1993, 96:19-27.
39. Farber K., Kettenmann H. Purinergic signaling and microglia. Pflugers Arch. 2006, 452:615-621.
40. Flatters S.J., Bennett G.J. Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: evidence for mitochondrial dysfunction. Pain 2006, 122:245-257.
41. Franchi L., Eigenbrod T., Munoz-Planillo R., Nunez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat. Immunol. 2009, 10:241-247.
42. Gabra B.H., Benrezzak O., Pheng L.H., Duta D., Daull P., Sirois P., Nantel F., Battistini B. Inhibition of type 1 diabetic hyperalgesia in streptozotocin-induced Wistar versus spontaneous gene-prone BB/Worchester rats: efficacy of a selective bradykinin B1 receptor antagonist. J. Neuropathol. Exp. Neurol. 2005, 64:782-789.
43. Ghilardi J.R., Rohrich H., Lindsay T.H., Sevcik M.A., Schwei M.J., Kubota K., Halvorson K.G., Poblete J., Chaplan S.R., Dubin A.E., Carruthers N.I., Swanson D., Kuskowski M., Flores C.M., Julius D., Mantyh P.W. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J. Neurosci. 2005, 25:3126-3131.
44. Ginhoux F., Greter M., Leboeuf M., Nandi S., See P., Gokhan S., Mehler M.F., Conway S.J., Ng L.G., Stanley E.R., Samokhvalov I.M., Merad M. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010, 330:841-845.
45. Gottfried-Blackmore A., Kaunzner U.W., Idoyaga J., Felger J.C., McEwen B.S., Bulloch K. Acute in vivo exposure to interferon-gamma enables resident brain dendritic cells to become effective antigen presenting cells. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:20918-20923.
46. Griffin R.S., Costigan M., Brenner G.J., Ma C.H., Scholz J., Moss A., Allchorne A.J., Stahl G.L., Woolf C.J. Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. J. Neurosci. 2007, 27:8699-8708.
47. Guasti L., Richardson D., Jhaveri M., Eldeeb K., Barrett D., Elphick M.R., Alexander S.P., Kendall D., Michael G.J., Chapman V. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol. Pain 2009, 5:35.
48. Hald A., Nedergaard S., Hansen R.R., Ding M., Heegaard A.M. Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain. Eur. J. Pain 2009, 13:138-145.
49. Hanisch U.K., Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 2007, 10:1387-1394.
50. Hathway G.J., Vega-Avelaira D., Moss A., Ingram R., Fitzgerald M. Brief, low frequency stimulation of rat peripheral C-fibres evokes prolonged microglial-induced central sensitization in adults but not in neonates. Pain 2009, 144:110-118.
51. Haynes S.E., Hollopeter G., Yang G., Kurpius D., Dailey M.E., Gan W.B., Julius D. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 2006, 9:1512-1519.
52. Herzberg U., Sagen J. Peripheral nerve exposure to HIV viral envelope protein gp120 induces neuropathic pain and spinal gliosis. J. Neuroimmunol. 2001, 116:29-39.
53. Hide I., Tanaka M., Inoue A., Nakajima K., Kohsaka S., Inoue K., Nakata Y. Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia. J. Neurochem. 2000, 75:965-972.
54. Honda S., Sasaki Y., Ohsawa K., Imai Y., Nakamura Y., Inoue K., Kohsaka S. Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors. J. Neurosci. 2001, 21:1975-1982.
55. Imai T., Hieshima K., Haskell C., Baba M., Nagira M., Nishimura M., Kakizaki M., Takagi S., Nomiyama H., Schall T.J., Yoshie O. Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 1997, 91:521-530.
56. Inoue K. Purinergic systems in microglia. Cell. Mol. Life Sci. 2008, 65:3074-3080.
57. Jack C.S., Arbour N., Manusow J., Montgrain V., Blain M., McCrea E., Shapiro A., Antel J.P. TLR signaling tailors innate immune responses in human microglia and astrocytes. J. Immunol. 2005, 175:4320-4330.
58. Ji R.R., Suter M.R. p38 MAPK, microglial signaling, and neuropathic pain. Mol. Pain 2007, 3:33.
59. Jin S.X., Zhuang Z.Y., Woolf C.J., Ji R.R. p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J. Neurosci. 2003, 23:4017-4022.
60. Kamoto Y., Sadato N., Yonekura Y., Tsuchida T., Uematsu H., Waki A., Uchida K., Baba H., Imura S., Konishi J. Visualization of the cervical spinal cord with FDG and high-resolution PET. J. Comput. Assist. Tomogr. 1998, 22:487-491.
61. Kawasaki Y., Xu Z.Z., Wang X., Park J.Y., Zhuang Z.Y., Tan P.H., Gao Y.J., Roy K., Corfas G., Lo E.H., Ji R.R. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat. Med. 2008, 14:331-336.
62. Kawasaki Y., Zhang L., Cheng J.K., Ji R.R. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J. Neurosci. 2008, 28:5189-5194.
63. Kim D., Kim M.A., Cho I.H., Kim M.S., Lee S., Jo E.K., Choi S.Y., Park K., Kim J.S., Akira S., Na H.S., Oh S.B., Lee S.J. A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J. Biol. Chem. 2007, 282:14975-14983.
64. Kim S.H., Chung J.M. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992, 50:355-363.
65. Knyihar-Csillik E., Rakic P., Csillik B. Transganglionic degenerative atrophy in the substantia gelatinosa of the spinal cord after peripheral nerve transection in rhesus monkeys. Cell Tissue Res. 1987, 247:599-604.
66. Koizumi S., Shigemoto-Mogami Y., Nasu-Tada K., Shinozaki Y., Ohsawa K., Tsuda M., Joshi B.V., Jacobson K.A., Kohsaka S., Inoue K. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 2007, 446:1091-1095.
67. Lacroix-Fralish M.L., Tawfik V.L., Nutile-McMenemy N., DeLeo J.A. Neuregulin 1 is a pronociceptive cytokine that is regulated by progesterone in the spinal cord: implications for sex specific pain modulation. Eur. J. Pain 2008, 12:94-103.
68. Lan L.S., Ping Y.J., Na W.L., Miao J., Cheng Q.Q., Ni M.Z., Lei L., Fang L.C., Guang R.C., Jin Z., Wei L. Down-regulation of Toll-like receptor 4 gene expression by short interfering RNA attenuates bone cancer pain in a rat model. Mol. Pain 2010, 6:2.
69. Lawson L.J., Perry V.H., Gordon S. Turnover of resident microglia in the normal adult mouse brain. Neuroscience 1992, 48:405-415.
70. Le C.V., Carreno S., Moisand A., Bordier C., Maridonneau-Parini I. Complement receptor 3 (CD11b/CD18) mediates type I and type II phagocytosis during nonopsonic and opsonic phagocytosis, respectively. J. Immunol. 2002, 169:2003-2009.
71. Ledeboer A., Jekich B.M., Sloane E.M., Mahoney J.H., Langer S.J., Milligan E.D., Martin D., Maier S.F., Johnson K.W., Leinwand L.A., Chavez R.A., Watkins L.R. Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats. Brain Behav. Immun. 2007, 21:686-698.
72. Ledeboer A., Sloane E.M., Milligan E.D., Frank M.G., Mahony J.H., Maier S.F., Watkins L.R. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 2005, 115:71-83.
73. Leger T., Grist J., D'Acquisto F., Clark A.K., Malcangio M. Glatiramer acetate attenuates neuropathic allodynia through modulation of adaptive immune cells. J. Neuroimmunol. 2011, 234:19-26.
74. Liao Y.H., Zhang G.H., Jia D., Wang P., Qian N.S., He F., Zeng X.T., He Y., Yang Y.L., Cao D.Y., Zhang Y., Wang D.S., Tao K.S., Gao C.J., Dou K.F. Spinal astrocytic activation contributes to mechanical allodynia in a mouse model of type 2 diabetes. Brain Res. 2011, 1368:324-335.
75. Lin C.S., Tsaur M.L., Chen C.C., Wang T.Y., Lin C.F., Lai Y.L., Hsu T.C., Pan Y.Y., Yang C.H., Cheng J.K. Chronic intrathecal infusion of minocycline prevents the development of spinal-nerve ligation-induced pain in rats. Reg. Anesth. Pain Med. 2007, 32:209-216.
76. Liu L., Rudin M., Kozlova E.N. Glial cell proliferation in the spinal cord after dorsal rhizotomy or sciatic nerve transection in the adult rat. Exp. Brain Res. 2000, 131:64-73.
77. Loram L.C., Harrison J.A., Sloane E.M., Hutchinson M.R., Sholar P., Taylor F.R., Berkelhammer D., Coats B.D., Poole S., Milligan E.D., Maier S.F., Rieger J., Watkins L.R. Enduring reversal of neuropathic pain by a single intrathecal injection of adenosine 2A receptor agonists: a novel therapy for neuropathic pain. J. Neurosci. 2009, 29:14015-14025.
78. Lu B., Rutledge B.J., Gu L., Fiorillo J., Lukacs N.W., Kunkel S.L., North R., Gerard C., Rollins B.J. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J. Exp. Med. 1998, 187:601-608.
79. Ludwig J., Binder A., Steinmann J., Wasner G., Baron R. Cytokine expression in serum and cerebrospinal fluid in non-inflammatory polyneuropathies. J. Neurol. Neurosurg. Psychiatry 2008, 79:1268-1273.
80. Maciejewski-Lenoir D., Chen S., Feng L., Maki R., Bacon K.B. Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia. J. Immunol. 1999, 163:1628-1635.
81. Maeda M., Tsuda M., Tozaki-Saitoh H., Inoue K., Kiyama H. Nerve injury-activated microglia engulf myelinated axons in a P2Y12 signaling-dependent manner in the dorsal horn. Glia 2010, 58:1838-1846.
82. Martinon F., Burns K., Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 2002, 10:417-426.
83. Mei L., Xiong W.C. Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat. Rev. Neurosci. 2008, 9:437-452.
84. Mildner A., Schmidt H., Nitsche M., Merkler D., Hanisch U.K., Mack M., Heikenwalder M., Bruck W., Priller J., Prinz M. Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat. Neurosci. 2007, 10:1544-1553.
85. Miller A.M., Stella N. Microglial cell migration stimulated by ATP and C5a involve distinct molecular mechanisms: quantification of migration by a novel near-infrared method. Glia 2009, 57:875-883.
86. Milligan E., Zapata V., Schoeniger D., Chacur M., Green P., Poole S., Martin D., Maier S.F., Watkins L.R. An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine. Eur. J. Neurosci. 2005, 22:2775-2782.
87. Milligan E.D., Langer S.J., Sloane E.M., He L., Wieseler-Frank J., O'Connor K., Martin D., Forsayeth J.R., Maier S.F., Johnson K., Chavez R.A., Leinwand L.A., Watkins L.R. Controlling pathological pain by adenovirally driven spinal production of the anti-inflammatory cytokine, interleukin-10. Eur. J. Neurosci. 2005, 21:2136-2148.
88. Milligan E.D., O'Connor K.A., Nguyen K.T., Armstrong C.B., Twining C., Gaykema R.P., Holguin A., Martin D., Maier S.F., Watkins L.R. Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines. J. Neurosci. 2001, 21:2808-2819.
89. Napoli I., Neumann H. Microglial clearance function in health and disease. Neuroscience 2009, 158:1030-1038.
90. Nimmerjahn A., Kirchhoff F., Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005, 308:1314-1318.
91. Nolte C., Moller T., Walter T., Kettenmann H. Complement 5a controls motility of murine microglial cells in vitro via activation of an inhibitory G-protein and the rearrangement of the actin cytoskeleton. Neuroscience 1996, 73:1091-1107.
92. Nutile-McMenemy N., Elfenbein A., DeLeo J.A. Minocycline decreases in vitro microglial motility, beta1-integrin, and Kv1.3 channel expression. J. Neurochem. 2007, 103:2035-2046.
93. Obata K., Katsura H., Miyoshi K., Kondo T., Yamanaka H., Kobayashi K., Dai Y., Fukuoka T., Akira S., Noguchi K. Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury. J. Neurochem. 2008, 105:2249-2259.
94. Obrosova I.G. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 2009, 6:638-647.
95. Ohsawa K., Irino Y., Nakamura Y., Akazawa C., Inoue K., Kohsaka S. Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis. Glia 2007, 55:604-616.
96. Olson J.K., Miller S.D. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J. Immunol. 2004, 173:3916-3924.
97. Opal S.M., DePalo V.A. Anti-inflammatory cytokines. Chest 2000, 117:1162-1172.
98. Orr A.G., Orr A.L., Li X.J., Gross R.E., Traynelis S.F. Adenosine A(2A) receptor mediates microglial process retraction. Nat. Neurosci. 2009, 12:872-878.
99. Pabbidi R.M., Cao D.S., Parihar A., Pauza M.E., Premkumar L.S. Direct role of streptozotocin in inducing thermal hyperalgesia by enhanced expression of transient receptor potential vanilloid 1 in sensory neurons. Mol. Pharmacol. 2008, 73:995-1004.
100. Perry V.H. A revised view of the central nervous system microenvironment and major histocompatibility complex class II antigen presentation. J. Neuroimmunol. 1998, 90:113-121.
101. Peters C.M., Ghilardi J.R., Keyser C.P., Kubota K., Lindsay T.H., Luger N.M., Mach D.B., Schwei M.J., Sevcik M.A., Mantyh P.W. Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain. Exp. Neurol. 2005, 193:85-100.
102. Peters C.M., Jimenez-Andrade J.M., Jonas B.M., Sevcik M.A., Koewler N.J., Ghilardi J.R., Wong G.Y., Mantyh P.W. Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells. Exp. Neurol. 2007, 203:42-54.
103. Polgar E., Hughes D.I., Arham A.Z., Todd A.J. Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain. J. Neurosci. 2005, 25:6658-6666.
104. Raghavendra V., Tanga F., DeLeo J.A. Inhibition of microglial activation attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J. Pharmacol. Exp. Ther. 2003, 306:624-630.
105. Raivich G., Moreno-Flores M.T., Moller J.C., Kreutzberg G.W. Inhibition of posttraumatic microglial proliferation in a genetic model of macrophage colony-stimulating factor deficiency in the mouse. Eur. J. Neurosci. 1994, 6:1615-1618.
106. Ransohoff R.M., Perry V.H. Microglial physiology: unique stimuli, specialized responses. Annu. Rev. Immunol. 2009, 27:119-145.
107. Romanovsky D., Cruz N.F., Dienel G.A., Dobretsov M. Mechanical hyperalgesia correlates with insulin deficiency in normoglycemic streptozotocin-treated rats. Neurobiol. Dis. 2006, 24:384-394.
108. Romero-Sandoval A., Nutile-McMenemy N., DeLeo J.A. Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury. Anesthesiology 2008, 108:722-734.
109. Romero-Sandoval E.A., Horvath R., Landry R.P., DeLeo J.A. Cannabinoid receptor type 2 activation induces a microglial anti-inflammatory phenotype and reduces migration via MKP induction and ERK dephosphorylation. Mol. Pain 2009, 5:25.
110. Schoenborn J.R., Wilson C.B. Regulation of interferon-gamma during innate and adaptive immune responses. Adv. Immunol. 2007, 96:41-101.
111. Schroder K., Hertzog P.J., Ravasi T., Hume D.A. Interferon-gamma: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 2004, 75:163-189.
112. Seltzer Z., Dubner R., Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990, 43:205-218.
113. Shigemoto-Mogami Y., Koizumi S., Tsuda M., Ohsawa K., Kohsaka S., Inoue K. Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse microglial cell line, MG-5. J. Neurochem. 2001, 78:1339-1349.
114. Shiratori M., Tozaki-Saitoh H., Yoshitake M., Tsuda M., Inoue K. P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways. J. Neurochem. 2010, 114(3):810-819.
115. Shoham S., Bejar C., Kovalev E., Weinstock M. Intracerebroventricular injection of streptozotocin causes neurotoxicity to myelin that contributes to spatial memory deficits in rats. Exp. Neurol. 2003, 184:1043-1052.
116. Soehnlein O., Lindbom L. Phagocyte partnership during the onset and resolution of inflammation. Nat. Rev. Immunol. 2010, 10:427-439.
117. Soulet D., Rivest S. Bone-marrow-derived microglia: myth or reality?. Curr. Opin. Pharmacol. 2008, 8:508-518.
118. Stevens B., Allen N.J., Vazquez L.E., Howell G.R., Christopherson K.S., Nouri N., Micheva K.D., Mehalow A.K., Huberman A.D., Stafford B., Sher A., Litke A.M., Lambris J.D., Smith S.J., John S.W., Barres B.A. The classical complement cascade mediates CNS synapse elimination. Cell 2007, 131:1164-1178.
119. Suh H.S., Kim M.O., Lee S.C. Inhibition of granulocyte-macrophage colony-stimulating factor signaling and microglial proliferation by anti-CD45RO: role of Hck tyrosine kinase and phosphatidylinositol 3-kinase/Akt. J. Immunol. 2005, 174:2712-2719.
120. Sung C.S., Wen Z.H., Chang W.K., Chan K.H., Ho S.T., Tsai S.K., Chang Y.C., Wong C.S. Inhibition of p38 mitogen-activated protein kinase attenuates interleukin-1beta-induced thermal hyperalgesia and inducible nitric oxide synthase expression in the spinal cord. J. Neurochem. 2005, 94:742-752.
121. Suter M.R., Berta T., Gao Y.J., Decosterd I., Ji R.R. Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury. Mol. Pain 2009, 5:53.
122. Svensson C.I., Marsala M., Westerlund A., Calcutt N.A., Campana W.M., Freshwater J.D., Catalano R., Feng Y., Protter A.A., Scott B., Yaksh T.L. Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing. J. Neurochem. 2003, 86:1534-1544.
123. Svensson M., Aldskogius H. Synaptic density of axotomized hypoglossal motorneurons following pharmacological blockade of the microglial cell proliferation. Exp. Neurol. 1993, 120:123-131.
124. Sweitzer S.M., Pahl J.L., DeLeo J.A. Propentofylline attenuates vincristine-induced peripheral neuropathy in the rat. Neurosci. Lett. 2006, 400:258-261.
125. Sweitzer S.M., White K.A., Dutta C., DeLeo J.A. The differential role of spinal MHC class II and cellular adhesion molecules in peripheral inflammatory versus neuropathic pain in rodents. J. Neuroimmunol. 2002, 125:82-93.
126. Talbot S., Chahmi E., Dias J.P., Couture R. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy. J. Neuroinflammation 2010, 7(1):36. 29.
127. Tanga F.Y., Nutile-McMenemy N., DeLeo J.A. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:5856-5861.
128. Thacker M.A., Clark A.K., Bishop T., Grist J., Yip P.K., Moon L.D., Thompson S.W., Marchand F., McMahon S.B. CCL2 is a key mediator of microglia activation in neuropathic pain states. Eur. J. Pain 2009, 13:263-272.
129. Tichauer J., Saud K., von B.R. Modulation by astrocytes of microglial cell-mediated neuroinflammation: effect on the activation of microglial signaling pathways. Neuroimmunomodulation 2007, 14:168-174.
130. Tozaki-Saitoh H., Tsuda M., Miyata H., Ueda K., Kohsaka S., Inoue K. P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. J. Neurosci. 2008, 28:4949-4956.
131. Trang T., Beggs S., Wan X., Salter M.W. P2X4-receptor-mediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase activation. J. Neurosci. 2009, 29:3518-3528.
132. Trapp B.D., Wujek J.R., Criste G.A., Jalabi W., Yin X., Kidd G.J., Stohlman S., Ransohoff R. Evidence for synaptic stripping by cortical microglia. Glia 2007, 55:360-368.
133. Tsuda M., Masuda T., Kitano J., Shimoyama H., Tozaki-Saitoh H., Inoue K. IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:8032-8037.
134. Tsuda M., Mizokoshi A., Shigemoto-Mogami Y., Koizumi S., Inoue K. Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain hypersensitivity following peripheral nerve injury. Glia 2004, 45:89-95.
135. Tsuda M., Shigemoto-Mogami Y., Koizumi S., Mizokoshi A., Kohsaka S., Salter M.W., Inoue K. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 2003, 424:778-783.
136. Tsuda M., Tozaki-Saitoh H., Inoue K. Pain and purinergic signaling. Brain Res. Rev. 2010, 63:222-232.
137. Tsuda M., Ueno H., Kataoka A., Tozaki-Saitoh H., Inoue K. Activation of dorsal horn microglia contributes to diabetes-induced tactile allodynia via extracellular signal-regulated protein kinase signaling. Glia 2008, 56:378-386.
138. Tsujino H., Kondo E., Fukuoka T., Dai Y., Tokunaga A., Miki K., Yonenobu K., Ochi T., Noguchi K. Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: a novel neuronal marker of nerve injury. Mol. Cell. Neurosci. 2000, 15:170-182.
139. Verge G.M., Milligan E.D., Maier S.F., Watkins L.R., Naeve G.S., Foster A.C. Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur. J. Neurosci. 2004, 20:1150-1160.
140. Wallace V.C., Blackbeard J., Segerdahl A.R., Hasnie F., Pheby T., McMahon S.B., Rice A.S. Characterization of rodent models of HIV-gp120 and anti-retroviral-associated neuropathic pain. Brain 2007, 130:2688-2702.
141. Wallace V.C., Blackbeard J., Pheby T., Segerdahl A.R., Davies M., Hasnie F., Hall S., McMahon S.B., Rice A.S. Pharmacological, behavioural and mechanistic analysis of HIV-1 gp120 induced painful neuropathy. Pain 2007, 133:47-63.
142. Wang W., Ji P., Dow K.E. Corticotropin-releasing hormone induces proliferation and TNF-alpha release in cultured rat microglia via MAP kinase signalling pathways. J. Neurochem. 2003, 84:189-195.
143. White F.A., Jung H., Miller R.J. Chemokines and the pathophysiology of neuropathic pain. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:20151-20158.
144. Wodarski R., Clark A.K., Grist J., Marchand F., Malcangio M. Gabapentin reverses microglial activation in the spinal cord of streptozotocin-induced diabetic rats. Eur. J. Pain 2009, 13(8):807-811.
145. Xu Z.Z., Zhang L., Liu T., Park J.Y., Berta T., Yang R., Serhan C.N., Ji R.R. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat. Med. 2010, 16(592-7):1p.
146. Yamamoto S., Nakajima K., Kohsaka S. Macrophage-colony stimulating factor as an inducer of microglial proliferation in axotomized rat facial nucleus. J. Neurochem. 2010, 115:1057-1067.
147. Yao J., Harvath L., Gilbert D.L., Colton C.A. Chemotaxis by a CNS macrophage, the microglia. J. Neurosci. Res. 1990, 27:36-42.
148. Zeilhofer H.U. Loss of glycinergic and GABAergic inhibition in chronic pain-contributions of inflammation and microglia. Int. Immunopharmacol. 2008, 8:182-187.
149. Zhang J., Shi X.Q., Echeverry S., Mogil J.S., De K.Y., Rivest S. Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain. J. Neurosci. 2007, 27:12396-12406.
150. Zhang R.X., Liu B., Wang L., Ren K., Qiao J.T., Berman B.M., Lao L. Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia. Pain 2005, 118:125-136.
151. Zheng F.Y., Xiao W.H., Bennett G.J. The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries. Neuroscience 2011, 176:447-454.
152. Zhuang Z.Y., Gerner P., Woolf C.J., Ji R.R. ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain 2005, 114:149-159.
153. Zhuang Z.Y., Kawasaki Y., Tan P.H., Wen Y.R., Huang J., Ji R.R. Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine. Brain Behav. Immun. 2007, 21:642-651.